Aim To make a research of rats with focal cerebral ischemia/reperfusion injury on pathological changes in brain and the changes of AQP4 and related proteins, in order to explore the relationship between AQP4 and brain edema. Methods Adult male SD rats, weighting 250~300 g, were randomly divided in-to Sham group and cerebral ischemia/reperfusion ( I/R) injury model group. The I/R model group was di-vided into the I/R-6 h, 12 h, 24 h, 48 h-four time point groups. The animal model of the right MCA is-chemia/reperfusion was established by suture method in mature SD rats. The nerve symptom score was con-ducted in the corresponding time points. Then, the permeability of brain tissue was detected by EB stai-ning;TTC staining was conducted to observe the cere-bral infarction volume;the dry wet weight method was used to detect the changes of brain water content; im-munohistochemical( IHC) , WB and RT-PCR were ap-plied to detect the expression of AQP4 , and the related factors at different time points of the model rats after is-chemia-reperfusion around infarcts. Results Com-pared with the Sham group, then ever function score of the rats in I/R model groups were much higher. With the increase of the reperfusion time, the cerebral in-farction volume, brain tissue permeability and the brain water content were also increased. IHC results showed that AQP4 expression gradually rose with widen distribution. WB and RT-PCR results verified the in-creasing level of AQP4 expression. The detection of the related proteins expression showed apparent changes. The expression of MMP-9 was increased, while the Oc-cludin and JAM-1 expression showed a decreasing trend. The I/R-48 h model group showed the most ob-vious differences in the expression of the related pro-teins and mRNA ( P <0. 01 vs Sham, respectively ) . Conclusion Accompanied with the aggravating cere-bral injury after cerebral ischemia/reperfusion, the ex-pression of AQP4 and MMP-9 level were activated, while the degradation of TJPs, Occludin and JAM-1, was increased. These factors are combined to make the formation of brain edema. This study makes a further research on the formation mechanism of the early stage for cerebral edema on I/R model and offers a potential for intervention in the filed of looking for a reliable drug therapy on cerebral edema.